Objective To investigate the effect of forkhead box C1(FOXC1)on the differentiation of human epidermal stem cells into sweat gland cells and its possible mechanism.Methods Epidermal stem cells were isolated and cultured from 7 patients who underwent circumcision in the Department of Urology of our hospital from January 2021 to June 2022.Cells were transfected with FOXC1 lentivirus plasmid,and the overexpression group,interference group and control group were set up respectively.The mRNA and protein expressions of FOXC1 were detected by real-time polymerase chain reaction(RT-PCR)and Western blot,respectively.Cell proliferation and colony formation rate were detected by MTT assay and Giemsa staining,respectively.The expression levels of matrix metalloproteinase 2(MMP-2)and MMP-9 in the culture medium were detected by enzyme-linked immunosorbent assay(ELISA).The Ca2+fluorescence intensity was detected by confocal laser scanning microscopy.The protein expressions of Cytokeratin 19(CK19),CK18,carcinoembryonic antigen(CEA),integrin-beta1(ITGB1)were detected by Western blot.Results Compared with those of the control group,the mRNA and protein expressions of FOXC1,cell proliferation level,colony formation rate,Ca2+fluorescence intensity,and protein expressions of MMP-2,MMP-9,and epidermal stem cell markers CK18 and CEA protein significantly increased,and protein expressions of ITGB1 and CK19 significantly decreased in overexpression group(P<0.05).The interference group yielded the different results.Conclusion FOXC1 can promote the phenotypic changes of epidermal stem cells being differentiated into sweat gland cells by promoting proliferation and upregulating Ca2+,MMP-2 and MMP-9.